Axonemal dynein light chain; Axonemal dynein light chain proteins play a dynamic role in flagellar and cilia motility. Eukaryotic cilia and flagella are complex organelles consisting of a core structure, the axoneme, which is composed of nine microtubule doublets forming a cylinder that surrounds a pair of central singlet microtubules. This ultra-structural arrangement seems to be one of the most stable micro-tubular assemblies known and is responsible for the flagellar and ciliary movement of a large number of organizms ranging from protozoan to mammals. This light chain interacts directly with the N-terminal half of the heavy chains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958660963 263 ESMTVHELRQAIVAMMNRKD------ELEEENGSLRNLLdgemehsAALRQEVDALRRKVTEQQE----RHATKVQALAR 332
Cdd:pfam10211 104 ESSVAFGMRKALQAEQGKAElekkiaDLEEEKEELEKQV-------AELKAKCEAIEKREEERRQaeekKHAEEIAFLKK 176

                          90
                  ....*....|.
gi 1958660963 333 ENEVLKVQLKK 343
Cdd:pfam10211 177 TNQQLKAQLER 187

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958660963 489 EWNVYRRYTEFRGLHHQLQSAFPQVRAYSFPPKKAIGNKDAKFVEERRKQLQSYLRSVMN-KVIQMVPEFA 558
Cdd:pfam00787   8 EWSVRRRYSDFVELHKKLLRKFPSVIIPPLPPKRWLGRYNEEFIEKRRKGLEQYLQRLLQhPELRNSEVLL 78

Axonemal dynein light chain; Axonemal dynein light chain proteins play a dynamic role in flagellar and cilia motility. Eukaryotic cilia and flagella are complex organelles consisting of a core structure, the axoneme, which is composed of nine microtubule doublets forming a cylinder that surrounds a pair of central singlet microtubules. This ultra-structural arrangement seems to be one of the most stable micro-tubular assemblies known and is responsible for the flagellar and ciliary movement of a large number of organizms ranging from protozoan to mammals. This light chain interacts directly with the N-terminal half of the heavy chains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958660963 263 ESMTVHELRQAIVAMMNRKD------ELEEENGSLRNLLdgemehsAALRQEVDALRRKVTEQQE----RHATKVQALAR 332
Cdd:pfam10211 104 ESSVAFGMRKALQAEQGKAElekkiaDLEEEKEELEKQV-------AELKAKCEAIEKREEERRQaeekKHAEEIAFLKK 176

                          90
                  ....*....|.
gi 1958660963 333 ENEVLKVQLKK 343
Cdd:pfam10211 177 TNQQLKAQLER 187

The phosphoinositide binding Phox Homology domain of KIF16B kinesin or Sorting Nexin 23; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. KIF16B, also called sorting nexin 23 (SNX23), is a family-3 kinesin which harbors an N-terminal kinesin motor domain containing ATP and microtubule binding sites, a ForkHead Associated (FHA) domain, and a C-terminal PX domain. The PX domain of KIF16B binds to phosphatidylinositol-3-phosphate (PI3P) in early endosomes and plays a role in the transport of early endosomes to the plus end of microtubules. By regulating early endosome plus end motility, KIF16B modulates the balance between recycling and degradation of receptors. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958660963 459 INVWIPSVFLRGKAANAYHVYQVYIRIKDDEWNVYRRYTEFRGLHHQLQSAFPQVRAYSFPPKKAIGNKDAKFVEERRKQ 538
Cdd:cd06874     1 IKITIPRYVLRGQGKDEHFEFEVKITVLDETWTVFRRYSRFRELHKTMKLKYPEVAALEFPPKKLFGNKSERVAKERRRQ 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1958660963 539 LQSYLRSVMNKVIQ-----MVPEFAANPKKETLVQLVPFF 573
Cdd:cd06874    81 LETYLRNFFSVCLKlpacpLYPKVGRTLSKATLCDFSPFF 120

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958660963 489 EWNVYRRYTEFRGLHHQLQSAFPQVRAYSFPPKKAIGNKDAKFVEERRKQLQSYLRSVMN-KVIQMVPEFA 558
Cdd:pfam00787   8 EWSVRRRYSDFVELHKKLLRKFPSVIIPPLPPKRWLGRYNEEFIEKRRKGLEQYLQRLLQhPELRNSEVLL 78

The phosphoinositide binding Phox Homology domain of Sorting Nexin 13; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX13, also called RGS-PX1, contains an N-terminal PXA domain, a regulator of G protein signaling (RGS) domain, a PX domain, and a C-terminal domain that is conserved in some SNXs. It specifically binds to the stimulatory subunit of the heterotrimeric G protein G(alpha)s, serving as its GTPase activating protein, through the RGS domain. It preferentially binds phosphatidylinositol-3-phosphate (PI3P) through the PX domain and is localized in early endosomes. SNX13 is involved in endosomal sorting of EGFR into multivesicular bodies (MVB) for delivery to the lysosome.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958660963 475 AYHVYQVYIRIKDDEWNVYRRYTEFRGLHHQLQSAFPQVRAYSFPPKKAIGNKDAKFVEERRKQLQSYLRSVMNKViqmv 554
Cdd:cd06873    26 AISVTRIYPNGQEESWHVYRRYSDFHDLHMRLKEKFPNLSKLSFPGKKTFNNLDRAFLEKRRKMLNQYLQSLLNPE---- 101

                          90
                  ....*....|...
gi 1958660963 555 pEFAANPKKETLV 567
Cdd:cd06873   102 -VLDANPGLQEIV 113

The phosphoinositide binding Phox Homology domain of the Imidazoline Receptor Antisera-Selected; The PX domain is a phosphoinositide binding (PI) module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Imidazoline Receptor Antisera-Selected (IRAS), also called nischarin, contains an N-terminal PX domain, leucine rich repeats, and a predicted coiled coil domain. The PX domain of IRAS binds to phosphatidylinositol-3-phosphate in membranes. Together with the coiled coil domain, it is essential for the localization of IRAS to endosomes. IRAS has been shown to interact with integrin and inhibit cell migration. Its interaction with alpha5 integrin causes a redistribution of the receptor from the cell surface to endosomal structures, suggesting that IRAS may function as a sorting nexin (SNX) which regulates the endosomal trafficking of integrin. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958660963 476 YHVYQVYIRIKDDEWNVYRRYTEFRGLHHQLqsafpqVRAYS-----FPPKKAIGNKDAKFVEERRKQLQSYLRSVMNKV 550
Cdd:cd06875    17 YTVYIIEVKVGSVEWTVKHRYSDFAELHDKL------VAEHKvdkdlLPPKKLIGNKSPSFVEKRRKELEIYLQTLLSFF 90

                  ....*.
gi 1958660963 551 IQMVPE 556
Cdd:cd06875    91 QKTMPR 96

The phosphoinositide binding Phox Homology domain of Sorting Nexin 16; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX16 contains a central PX domain followed by a coiled-coil region. SNX16 is localized in early and recycling endosomes through the binding of its PX domain to phosphatidylinositol-3-phosphate (PI3P). It plays a role in epidermal growth factor (EGF) signaling by regulating EGF receptor membrane trafficking.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958660963 478 VYQVYIRIK-DDEWNVYRRYTEFRGLHHQLQSAFPQVRaYSFPPKKAIG-NKDAKFVEERRKQLQSYLRSVM 547
Cdd:cd07276    22 VYKIRVENKvGDSWFVFRRYTDFVRLNDKLKQMFPGFR-LSLPPKRWFKdNFDPDFLEERQLGLQAFVNNIM 92

The phosphoinositide binding Phox Homology domain of Sorting Nexins 1 and 2; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. This subfamily consists of SNX1, SNX2, and similar proteins. They harbor a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. Both domains have been shown to determine the specific membrane-targeting of SNX1. SNX1 and SNX2 are components of the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi. The retromer consists of a cargo-recognition subcomplex and a subcomplex formed by a dimer of sorting nexins (SNX1 and/or SNX2), which ensures effcient cargo sorting by facilitating proper membrane localization of the cargo-recognition subcomplex.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958660963 470 GKAANAYHVYQVYIR-----IKDDEWNVYRRYTEFRGLHHQLQSAFPQVRAYSFPPKKAIGNKDAK--FVEERRKQLQSY 542
Cdd:cd06859    12 GDGMSAYVVYRVTTKtnlpdFKKSEFSVLRRYSDFLWLYERLVEKYPGRIVPPPPEKQAVGRFKVKfeFIEKRRAALERF 91

                  ....*.
gi 1958660963 543 LRSVMN 548
Cdd:cd06859    92 LRRIAA 97

The phosphoinositide binding Phox Homology Domain of Cytokine-Independent Survival Kinase; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Cytokine-independent survival kinase (CISK), also called Serum- and Glucocorticoid-induced Kinase 3 (SGK3), plays a role in cell growth and survival. It is expressed in most tissues and is most abundant in the embryo and adult heart and spleen. It was originally discovered in a screen for antiapoptotic genes. It phosphorylates and inhibits the proapoptotic proteins, Bad and FKHRL1. CISK/SGK3 also regulates many transporters, ion channels, and receptors. It plays a critical role in hair follicle morphogenesis and hair cycling. N-terminal to a catalytic kinase domain, CISK contains a PX domain which binds highly phosphorylated PIs, directs membrane localization, and regulates the enzyme's activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958660963 476 YHVYQVYIRIKDDEWNVYRRYTEFRGLHHQLQSAFPQVrAYSFPPKKAIGNK-DAKFVEERRKQLQSYLRSVM--NKVIQ 552
Cdd:cd06870    20 FTVYKVVVSVGRSSWFVFRRYAEFDKLYESLKKQFPAS-NLKIPGKRLFGNNfDPDFIKQRRAGLDEFIQRLVsdPKLLN 98

                  ....*..
gi 1958660963 553 MvPEFAA 559
Cdd:cd06870    99 H-PDVRA 104

The phosphoinositide binding Phox Homology Domain of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They are also involved in the regulation of clathrin-mediated membrane trafficking as well as ATP-dependent priming of neurosecretory granule exocytosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. Class II PI3Ks include three vertebrate isoforms (alpha, beta, and gamma), the Drosophila PI3K_68D, and similar proteins.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958660963 474 NAYHVY--QVYIRIKDDEWNVYRRYTEFRGLHHQLQSAFPQVRAYSFPPKKAIGNKDAKFVEERRK-QLQSYLRSVMN 548
Cdd:cd06883    14 EKYYIYvvKVTRENQTEPSFVFRTFEEFQELHNKLSLLFPSLKLPSFPARVVLGRSHIKQVAERRKiELNSYLKSLFN 91

The phosphoinositide binding Phox Homology domain of Sorting Nexin 4; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX4 is involved in recycling traffic from the sorting endosome (post-Golgi endosome) back to the late Golgi. It shows a similar domain architecture as SNX1-2, among others, containing a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. SNX4 is implicated in the regulation of plasma membrane receptor trafficking and interacts with receptors for EGF, insulin, platelet-derived growth factor and the long form of the leptin receptor.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958660963 476 YHVYQVYIRIKDDEW---------NVYRRYTEFRGLHHQLQSAFPQVRAYSFPPKKA--------IGNKDAKFVEERRKQ 538
Cdd:cd06864    23 YTVYLIETKIVEHESeeglskklsSLWRRYSEFELLRNYLVVTYPYVIVPPLPEKRAmfmwqklsSDTFDPDFVERRRAG 102

                  ....*...
gi 1958660963 539 LQSYLRSV 546
Cdd:cd06864   103 LENFLLRV 110

The phosphoinositide binding Phox Homology domain of Sorting Nexin 2; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX2 is a component of the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi. The retromer consists of a cargo-recognition subcomplex and a subcomplex formed by a dimer of sorting nexins (SNX1 and/or SNX2), which ensures efficient cargo sorting by facilitating proper membrane localization of the cargo-recognition subcomplex. Similar to SNX1, SNX2 contains a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. The PX domain of SNX2 preferentially binds phosphatidylinositol-3-phosphate (PI3P), but not PI(3,4,5)P3. Studies on mice deficient with SNX1 and/or SNX2 suggest that they provide an essential function in embryogenesis and are functionally redundant.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958660963 470 GKAANAYHVYQVYIR-----IKDDEWNVYRRYTEFRGLHHQLQSAFPQVrAYSFPP----------KKAIGNKDA---KF 531
Cdd:cd07282    12 GDGMNAYMAYRVTTKtslsmFSRSEFSVRRRFSDFLGLHSKLASKYLHV-GYIVPPapeksivgmtKVKVGKEDSsstEF 90

                          90       100
                  ....*....|....*....|....*.
gi 1958660963 532 VEERRKQLQSYL-RSVMNKVIQMVPE 556
Cdd:cd07282    91 VEKRRAALERYLqRTVKHPTLLQDPD 116

The phosphoinositide binding Phox Homology domain of uncharacterized SNX19-like plant proteins; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to PI-enriched membranes. Members in this subfamily are uncharacterized plant proteins containing an N-terminal PXA domain, a central PX domain, and a C-terminal domain that is conserved in some sorting nexins (SNXs). This is the same domain architecture found in SNX19. SNX13 and SNX14 also contain these three domains but also contain a regulator of G protein signaling (RGS) domain in between the PXA and PX domains. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958660963 479 YQVY-IRIKDDE---WNVYRRYTEFRGLHHQLQSaFPQVrAYSFPPKKAIGNK-DAKFVEERRKQLQSYLRSVMnkVIQM 553
Cdd:cd06872    18 FAVYsVAVTDNEnetWVVKRRFRNFETLHRRLKE-VPKY-NLELPPKRFLSSSlDGAFIEERCKLLDKYLKDLL--VIEK 93

                  ....*
gi 1958660963 554 VPEFA 558
Cdd:cd06872    94 VAESH 98

The phosphoinositide binding Phox Homology Domain of the Alpha Isoform of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. The class II alpha isoform, PI3K-C2alpha, plays key roles in clathrin assembly and clathrin-mediated membrane trafficking, insulin signaling, vascular smooth muscle contraction, and the priming of neurosecretory granule exocytosis. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958660963 465 SVFLRGKAANAYHVYQVYIRI----KDDEWNVYRRYTEFRGLHHQLQSAFPQVRAYSFPPKKAIGNKDAKFVEERRK-QL 539
Cdd:cd07289     3 SVFTYHKRYNPDKHYIYVVRIlregQIEPSFVFRTFDEFQELHNKLSILFPLWKLPGFPNKMVLGRTHIKDVAAKRKvEL 82

                  ....*....
gi 1958660963 540 QSYLRSVMN 548
Cdd:cd07289    83 NSYIQSLMN 91

The phosphoinositide binding Phox Homology domain of Sorting Nexins 17 and 31; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Members of this subfamily include sorting nexin 17 (SNX17), SNX31, and similar proteins. They contain an N-terminal PX domain followed by a truncated FERM (4.1, ezrin, radixin, and moesin) domain and a unique C-terminal region. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX17 is known to regulate the trafficking and processing of a number of proteins. It binds some members of the low-density lipoprotein receptor (LDLR) family such as LDLR, VLDLR, ApoER2, and others, regulating their endocytosis. It also binds P-selectin and may regulate its lysosomal degradation. SNX17 is highly expressed in neurons. It binds amyloid precursor protein (APP) and may be involved in its intracellular trafficking and processing to amyloid beta peptide, which plays a central role in the pathogenesis of Alzheimer's disease. The biological function of SNX31 is unknown.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958660963 463 IP-SVFLRGKAANAYHVYQVYIRikddewNVYR---RYTEFRGLHHQLQSAFPQVRAYSFPPKKaIGNKDAKFVEERRKQ 538
Cdd:cd06885     4 IPdTQELSDEGGSTYVAYNIHIN------GVLHcsvRYSQLHGLNEQLKKEFGNRKLPPFPPKK-LLPLTPAQLEERRLQ 76

                  ....*...
gi 1958660963 539 LQSYLRSV 546
Cdd:cd06885    77 LEKYLQAV 84

The phosphoinositide binding Phox Homology domain of Sorting Nexin 14; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX14 may be involved in recruiting other proteins to the membrane via protein-protein and protein-ligand interaction. It is expressed in the embryonic nervous system of mice, and is co-expressed in the motoneurons and the anterior pituary with Islet-1. SNX14 shows a similar domain architecture as SNX13, containing an N-terminal PXA domain, a regulator of G protein signaling (RGS) domain, a PX domain, and a C-terminal domain that is conserved in some SNXs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958660963 460 NVWIPSVFLRGKAANAYHVYqVYI--------RIKDDE---WNVYRRYTEFRGLHHQLQSAFPQVRAYSFPPKKAIGNKD 528
Cdd:cd06877     4 RVSIPYVEMRRDPSNGERIY-VFCieverndrRAKGHEpqhWSVLRRYNEFYVLESKLTEFHGEFPDAPLPSRRIFGPKS 82

                          90       100
                  ....*....|....*....|.
gi 1958660963 529 AKFVEERRKQLQSYLRSVMNK 549
Cdd:cd06877    83 YEFLESKREIFEEFLQKLLQK 103

The phosphoinositide binding Phox Homology domain of Sorting Nexin 15; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX15 contains an N-terminal PX domain and a C-terminal Microtubule Interacting and Trafficking (MIT) domain. It plays a role in protein trafficking processes in the endocytic pathway and the trans-Golgi network. The PX domain of SNX15 interacts with the PDGF receptor and is responsible for the membrane association of the protein.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958660963 471 KAANAYHVYQVYIRIKD----DEWNVYRRYTEFRGLHHQL----------QSAFPqvraySFPPKKAIGNKDAKFVEERR 536
Cdd:cd07288    15 KGYTEYKVTAQFISKKQpedvKEVVVWKRYSDLKKLHGELaythrnlfrrQEEFP-----PFPRAQVFGRFEAAVIEERR 89

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1958660963 537 KQLQSYLRSVMNkviqmVPEFAANPkketlvQLVPFFVD 575
Cdd:cd07288    90 NAAEAMLLFTVN-----IPALYNSP------QLKEFFRD 117

The phosphoinositide binding Phox Homology Domain of Class II Phosphoinositide 3-Kinases similar to the Drosophila PI3K_68D protein; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. PI3K_68D is a novel PI3K which is widely expressed throughout the Drosophila life cycle. In vitro, it has been shown to phosphorylate PI and PI4P. It is involved in signaling pathways that affect pattern formation of Drosophila wings.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958660963 476 YHVYQVYI--RIKDDEWNVYRRYTEFRGLHHQLQSAFPQVRAYSFPPKKAIGNKDAKFVEERRKQ-LQSYLRSVMnkviQ 552
Cdd:cd06884    18 YYVYVVEVtrENQASPQHVFRTYKEFLELYQKLCRKFPLAKLHPLSTGSHVGRSNIKSVAEKRKQdIQQFLNSLF----K 93

                  ....*.
gi 1958660963 553 MVPEFA 558
Cdd:cd06884    94 MAEEVS 99

The phosphoinositide binding Phox Homology domain of uncharacterized fungal proteins; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to PI-enriched membranes. Members in this subfamily are uncharacterized fungal proteins containing a PX domain. PX domain harboring proteins have been implicated in highly diverse functions such as cell signaling, vesicular trafficking, protein sorting, lipid modification, cell polarity and division, activation of T and B cells, and cell survival. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958660963 477 HVYQVYIRIKDDEWN-----VYRRYTEFRGLHHQLQSAFPQVRAYSFPPKKaignkdaKFVEER-RKQLQSYLRSVMNkv 550
Cdd:cd06869    32 HHYEFIIRVRREGEEyrtiyVARRYSDFKKLHHDLKKEFPGKKLPKLPHKD-------KLPREKlRLSLRQYLRSLLK-- 102

                  ....*...
gi 1958660963 551 iqmVPEFA 558
Cdd:cd06869   103 ---DPEVA 107

The phosphoinositide binding Phox Homology Domain of the Beta Isoform of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. The class II beta isoform, PI3K-C2beta, contributes to the migration and survival of cancer cells. It regulates Rac activity and impacts membrane ruffling, cell motility, and cadherin-mediated cell-cell adhesion. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958660963 492 VYRRYTEFRGLHHQLQSAFPQVRAYSFPPKKAIGNKDAKFVEERRK-QLQSYLRSVMNKviqmVPEFA 558
Cdd:cd07290    34 VQRTFEEFQELHNKLRLLFPSSKLPSFPSRFVIGRSRGEAVAERRKeELNGYIWHLIHA----PPEVA 97

The phosphoinositide binding Phox Homology domain of fungal Sorting Nexins 41 and 42; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. SNX41 and SNX42 (also called Atg20p) form dimers with SNX4, and are required in protein recycling from the sorting endosome (post-Golgi endosome) back to the late Golgi in yeast.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958660963 479 YQVY-IRIKDDEwnVYRRYTEFRGLHHQLQSAFPQVRAYSFPPKKAIGN---------KDAKFVEERRKQLQSYLR 544
Cdd:cd06867    18 YIVYvIRLGGSE--VKRRYSEFESLRKNLTRLYPTLIIPPIPEKHSLKDyakkpskakNDAKIIERRKRMLQRFLN 91

The phosphoinositide binding Phox Homology domain of Sorting Nexins 9 and 18; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. This subfamily consists of SNX9, SNX18, and similar proteins. They contain an N-terminal Src Homology 3 (SH3) domain, a PX domain, and a C-terminal Bin/Amphiphysin/Rvs (BAR) domain. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958660963 492 VYRRYTEFRGLHHQLQSAFPQVRAYSFPPKKAIGNKDAKFVEERRKQLQSYlrsvMNKVIQ 552
Cdd:cd06862    34 VSRRYKHFDWLYERLVEKYSCIAIPPLPEKQVTGRFEEDFIEKRRERLELW----MNRLAR 90

The phosphoinositide binding Phox Homology domain of Sorting Nexin 18; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX18, like SNX9, contains an N-terminal Src Homology 3 (SH3) domain, a PX domain, and a C-terminal Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature. The PX-BAR structural unit helps determine specific membrane localization. SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1958660963 492 VYRRYTEFRGLHHQLQSAFPQVRAYSFPPKKAIGNKDAKFVEERRKQL 539
Cdd:cd07286    34 VHRRYKHFDWLYARLAEKFPVISVPHIPEKQATGRFEEDFISKRRKGL 81